The paramyoviruses are enveloped, negative-sense, non-segmented single stranded RNA viruses whose members can be extremely infectious, prevalent and disease causing. Examples include measles, mumps, respiratory syncytial virus and the parainfluenza viruses. Concerted efforts are being organized by the World Health Organization (WHO) to try to eradicate paramyxoviruses such as the measles virus. Other paramyxoviruses, such as the Newcastle disease, virus wreak havoc on farm animal populations.
In the United States, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) types 1, 2 3, and 4, are the major cause of hospitalization for respiratory illness in young children as well as in adults. For example, RSV and PIV together account for the majority of cases of bronchiolitis and croup in children. Likewise, RSV and PIV, account for nearly half of the cases of pneumonia and flu-like illness in children. In addition, both viruses can be transmitted via aerosol droplets and thus contribute to nosocomial infections.
Attempts to alleviate the impact of RSV and PIV on human health and on the world economy has been ongoing for more than 30 years with little success. For example, vaccine development in RSV was hampered early on by disappointing results with a formalin inactivated whole virus RSV vaccine. In this incident, subjects immunized with formalin inactivated whole virus contracted more severe disease following immunization. See Kim et al, Am. J. Epidemiol. 89:422-434 (1969). Previous attempts to make efficacious formaldehyde-inactivated PIV and RSV vaccine had failed to provide appropriate protection against infection. See Chin, J., et al., Am. J. Epidemiol. 89:449-463 (1969).
Currently two live attenuated vaccine candidates, a cold-passage derivative (cp45) of PIV3 (JS strain) and a bovine parainfluenza virus type 3 have been evaluated in clinical trials. See Jones, T., Current Opinion in Investigational Drugs, 2(7):890-892 (2001). As a result, cp45 is considered a promising PIV3 vaccine.
Another important aspect of RSV and PIV research remains prevention of disease complications in elderly people or in those with existing medical conditions such as pneumonia and lower respiratory tract infections. In this regard, there have been attempts to develop vector-based and purified protein antigens for administration to affected patient populations. See Crowe, J. E., et al. Virus Genes 13(3): 26-273 (1996).
A variety of vectors have been examined for their ability to incorporate and express heterologous genes of paramyxoviridae family viruses. These include, for example, wild type vaccinia or an attenuated Modified Ankara vaccinia (MVA) (Durbin et al., Vaccine 16:1234-1330 (1998); Elango, N., et al. Proc. Natl. Acad. Sci. USA 83:1906-1910 (1986)) replication-competent human adenovirus vector (Mittal S. K., et al., Intervirology 41(6):253-260 (1998)), Vesicular Stomatitis virus (VSV) (Kahn S. J., J. Virol 75(22):11079-87 (2001)), Semliki Forest virus (SFV) ((Peroulis, I., et al., Archives of Virology, 144:107-116 (1999), human PIV3 itself as a potential vector carrying PIV1/2 or measles virus genome (Skiadopoulos M. H., et al. Virology 29(1): 136-152 (2002)) and bovine PIV3 carrying human PIV3 genome (Haller A. A., et al. J. Virology 74(24):11626-35 (2000)). Preclinical studies with all the above vectors have showed promising protection efficacy against the corresponding pathogens.
In spite of the prevalence and severity of RSV and PIV disease and the numerous previous attempts to produce a vaccine, no immunogenic composition presently exists to prevent these infections. Therefore, a need exists for immunogenic compositions and methods of inducing protective immunity to RSV, PIV and other paramyxoviruses.